tbuckley/cabot-search huggingface dataset:
Machine learning for diagnosis of myocardial infarction using cardiac troponin concentrations
Authors: Dimitrios Doudesis, Kuan Ken Lee, Jasper Boeddinghaus, Anda Bularga, Amy V. Ferry, Chris Tuck, Matthew T. H. Lowry, Pedro Lopez-Ayala, Thomas Nestelberger, Luca Koechlin, Miguel O. Bernabeu, Lis Neubeck, Atul Anand, Karen Schulz, Fred S. Apple, William Parsonage, Jaimi H. Greenslade, Louise Cullen, John W. Pickering, Martin P. Than, Alasdair Gray, Christian Mueller, Nicholas L. Mills, A. Mark Richards, Chris Pemberton, Richard W. Troughton, Sally J. Aldous, Anthony F. T. Brown, Emily Dalton, Chris Hammett, Tracey Hawkins, Shanen O’Kane, Kate Parke, Kimberley Ryan, Jessica Schluter, Karin Wild, Desiree Wussler, Òscar Miró, F. Javier Martin-Sanchez, Dagmar I. Keller, Michael Christ, Andreas Buser, Maria Rubini Giménez, Stephanie Barker, Jennifer Blades, Andrew R. Chapman, Takeshi Fujisawa, Dorien M. Kimenai, Jeremy Leung, Ziwen Li, Michael McDermott, David E. Newby, Stacey D. Schulberg, Anoop S. V. Shah, Andrew Sorbie, Grace Soutar, Fiona E. Strachan, Caelan Taggart, Daniel Perez Vicencio, Yiqing Wang, Ryan Wereski, Kelly Williams, Christopher J. Weir, Colin Berry, Alan Reid, Donogh Maguire, Paul O. Collinson, Yader Sandoval, Stephen W. Smith
Journal: Nature Medicine (2023)

Abstract Although guidelines recommend fixed cardiac troponin thresholds for the diagnosis of myocardial infarction, troponin concentrations are influenced by age, sex, comorbidities and time from symptom onset. To improve diagnosis, we developed machine learning models that integrate cardiac troponin concentrations at presentation or on serial testing with clinical features and compute the Collaboration for the Diagnosis and Evaluation of Acute Coronary Syndrome (CoDE-ACS) score (0–100) that corresponds to an individual’s probability of myocardial infarction. The models were trained on data from 10,038 patients (48% women), and their performance was externally validated using data from 10,286 patients (35% women) from seven cohorts. CoDE-ACS had excellent discrimination for myocardial infarction (area under curve, 0.953; 95% confidence interval, 0.947–0.958), performed well across subgroups and identified more patients at presentation as low probability of having myocardial infarction than fixed cardiac troponin thresholds (61 versus 27%) with a similar negative predictive value and fewer as high probability of having myocardial infarction (10 versus 16%) with a greater positive predictive value. Patients identified as having a low probability of myocardial infarction had a lower rate of cardiac death than those with intermediate or high probability 30 days (0.1 versus 0.5 and 1.8%) and 1 year (0.3 versus 2.8 and 4.2%; P &lt; 0.001 for both) from patient presentation. CoDE-ACS used as a clinical decision support system has the potential to reduce hospital admissions and have major benefits for patients and health care providers.
Accelerated waning of the humoral response to COVID-19 vaccines in obesity
Authors: Agatha A van der Klaauw, Emily C Horner, Pehuén Pereyra-Gerber, Utkarsh Agrawal, William S Foster, Sarah Spencer, Bensi Vergese, Miriam Smith, Elana Henning, Isobel D Ramsay, Jack A Smith, Stephane M Guillaume, Hayley J Sharpe, Iain M Hay, Sam Thompson, Silvia Innocentin, Lucy H Booth, Chris Robertson, Colin McCowan, Steven Kerr, Thomas E Mulroney, Martin J O'Reilly, Thevinya P Gurugama, Lihinya P Gurugama, Maria A Rust, Alex Ferreira, Soraya Ebrahimi, Lourdes Ceron-Gutierrez, Jacopo Scotucci, Barbara Kronsteiner, Susanna J Dunachie, Paul Klenerman, Adrian J Park, Francesco Rubino, Abigail A Lamikanra, Hannah Stark, Nathalie Kingston, Lise Estcourt, Heli Harvala, David J Roberts, Rainer Doffinger, Michelle A Linterman, Nicholas J Matheson, Aziz Sheikh, I Sadaf Farooqi, James E D Thaventhiran
Journal: Nature Medicine (2023)

Obesity is associated with an increased risk of severe Coronavirus Disease 2019 (COVID-19) infection and mortality. COVID-19 vaccines reduce the risk of serious COVID-19 outcomes; however, their effectiveness in people with obesity is incompletely understood. We studied the relationship among body mass index (BMI), hospitalization and mortality due to COVID-19 among 3.6 million people in Scotland using the Early Pandemic Evaluation and Enhanced Surveillance of COVID-19 (EAVE II) surveillance platform. We found that vaccinated individuals with severe obesity (BMI > 40 kg/m
A sense-antisense RNA interaction promotes breast cancer metastasis via regulation of NQO1 expression
Authors: Bruce Culbertson, Kristle Garcia, Daniel Markett, Hosseinali Asgharian, Li Chen, Lisa Fish, Albertas Navickas, Johnny Yu, Brian Woo, Arjun Scott Nanda, Benedict Choi, Shaopu Zhou, Joshua Rabinowitz, Hani Goodarzi
Journal: Nature Cancer (2023)

Abstract Antisense RNAs are ubiquitous in human cells, yet their role is largely unexplored. Here we profiled antisense RNAs in the MDA-MB-231 breast cancer cell line and its highly lung metastatic derivative. We identified one antisense RNA that drives cancer progression by upregulating the redox enzyme NADPH quinone dehydrogenase 1 (NQO1), and named it NQO1-AS. Knockdown of either NQO1 or NQO1-AS reduced lung colonization in a mouse model, and investigation into the role of NQO1 indicated that it is broadly protective against oxidative damage and ferroptosis. Breast cancer cells in the lung are dependent on this pathway, and this dependence can be exploited therapeutically by inducing ferroptosis while inhibiting NQO1. Together, our findings establish a role for NQO1-AS in the progression of breast cancer by regulating its sense mRNA post-transcriptionally. Because breast cancer predominantly affects females, the disease models used in this study are of female origin and the results are primarily applicable to females.
ARG1-expressing microglia show a distinct molecular signature and modulate postnatal development and function of the mouse brain
Authors: Vassilis Stratoulias, Rocío Ruiz, Shigeaki Kanatani, Ahmed M Osman, Lily Keane, Jose A Armengol, Antonio Rodríguez-Moreno, Adriana-Natalia Murgoci, Irene García-Domínguez, Isabel Alonso-Bellido, Fernando González Ibáñez, Katherine Picard, Guillermo Vázquez-Cabrera, Mercedes Posada-Pérez, Nathalie Vernoux, Dario Tejera, Kathleen Grabert, Mathilde Cheray, Patricia González-Rodríguez, Eva M Pérez-Villegas, Irene Martínez-Gallego, Alejandro Lastra-Romero, David Brodin, Javier Avila-Cariño, Yang Cao, Mikko Airavaara, Per Uhlén, Michael T Heneka, Marie-Ève Tremblay, Klas Blomgren, Jose L Venero, Bertrand Joseph
Journal: Nature Neuroscience (2023)

Molecular diversity of microglia, the resident immune cells in the CNS, is reported. Whether microglial subsets characterized by the expression of specific proteins constitute subtypes with distinct functions has not been fully elucidated. Here we describe a microglial subtype expressing the enzyme arginase-1 (ARG1; that is, ARG1+ microglia) that is found predominantly in the basal forebrain and ventral striatum during early postnatal mouse development. ARG1+ microglia are enriched in phagocytic inclusions and exhibit a distinct molecular signature, including upregulation of genes such as Apoe, Clec7a, Igf1, Lgals3 and Mgl2, compared to ARG1- microglia. Microglial-specific knockdown of Arg1 results in deficient cholinergic innervation and impaired dendritic spine maturation in the hippocampus where cholinergic neurons project, which in turn results in impaired long-term potentiation and cognitive behavioral deficiencies in female mice. Our results expand on microglia diversity and provide insights into microglia subtype-specific functions.
Mobile element variation contributes to population-specific genome diversification, gene regulation and disease risk
Authors: Shohei Kojima, Satoshi Koyama, Mirei Ka, Yuka Saito, Erica H. Parrish, Mikiko Endo, Sadaaki Takata, Misaki Mizukoshi, Keiko Hikino, Atsushi Takeda, Asami F. Gelinas, Steven M. Heaton, Rie Koide, Anselmo J. Kamada, Michiya Noguchi, Michiaki Hamada, Koichi Matsuda, Yuji Yamanashi, Yoichi Furukawa, Takayuki Morisaki, Yoshinori Murakami, Kaori Muto, Akiko Nagai, Wataru Obara, Ken Yamaji, Kazuhisa Takahashi, Satoshi Asai, Yasuo Takahashi, Takao Suzuki, Nobuaki Sinozaki, Hiroki Yamaguchi, Shiro Minami, Shigeo Murayama, Kozo Yoshimori, Satoshi Nagayama, Daisuke Obata, Masahiko Higashiyama, Akihide Masumoto, Yukihiro Koretsune, Yoichiro Kamatani, Yasuhiro Murakawa, Kazuyoshi Ishigaki, Yukio Nakamura, Kaoru Ito, Chikashi Terao, Yukihide Momozawa, Nicholas F. Parrish
Journal: Nature Genetics (2023)
GAP43-dependent mitochondria transfer from astrocytes enhances glioblastoma tumorigenicity
Authors: Dionysios C. Watson, Defne Bayik, Simon Storevik, Shannon Sherwin Moreino, Samuel A. Sprowls, Jianhua Han, Mina Thue Augustsson, Adam Lauko, Palavalasa Sravya, Gro Vatne Røsland, Katie Troike, Karl Johan Tronstad, Sabrina Wang, Katharina Sarnow, Kristen Kay, Taral R. Lunavat, Daniel J. Silver, Sahil Dayal, Justin Vareecal Joseph, Erin Mulkearns-Hubert, Lars Andreas Rømo Ystaas, Gauravi Deshpande, Joris Guyon, Yadi Zhou, Capucine R. Magaut, Juliana Seder, Laura Neises, Sarah E. Williford, Johannes Meiser, Andrew J. Scott, Peter Sajjakulnukit, Jason A. Mears, Rolf Bjerkvig, Abhishek Chakraborty, Thomas Daubon, Feixiong Cheng, Costas A. Lyssiotis, Daniel R. Wahl, Anita B. Hjelmeland, Jubayer A. Hossain, Hrvoje Miletic, Justin D. Lathia
Journal: Nature Cancer (2023)

The transfer of intact mitochondria between heterogeneous cell types has been confirmed in various settings, including cancer. However, the functional implications of mitochondria transfer on tumor biology are poorly understood. Here we show that mitochondria transfer is a prevalent phenomenon in glioblastoma (GBM), the most frequent and malignant primary brain tumor. We identified horizontal mitochondria transfer from astrocytes as a mechanism that enhances tumorigenesis in GBM. This transfer is dependent on network-forming intercellular connections between GBM cells and astrocytes, which are facilitated by growth-associated protein 43 (GAP43), a protein involved in neuron axon regeneration and astrocyte reactivity. The acquisition of astrocyte mitochondria drives an increase in mitochondrial respiration and upregulation of metabolic pathways linked to proliferation and tumorigenicity. Functionally, uptake of astrocyte mitochondria promotes cell cycle progression to proliferative G2/M phases and enhances self-renewal and tumorigenicity of GBM. Collectively, our findings reveal a host-tumor interaction that drives proliferation and self-renewal of cancer cells, providing opportunities for therapeutic development.
EARLY DETECTION AND SCREENING FOR MULTIPLE MYELOMA PRECURSORS
Authors: S. Thorsteinsdottir
Journal: HemaSphere (2023)

Monoclonal gammopaty of undetermined significance (MGUS) and smoldering multiple myeloma (SMM) are asymptomatic precursors of multiple myeloma (MM). Emerging data from clinical trials indicate that initiation of treatment at the stage of high-risk SMM can improve outcomes in MM. Currently there is no established screening for MM precursors and most MM patients are therefore diagnosed after the development of symptomatic end-organ damage. The Iceland screens, treats, or prevents multiple myeloma (iStopMM) study (ClinicalTrials.gov #NCT03327597) is a nationwide screening study investigating the benefits and harms of screening for MM precursor conditions. All individuals residing in Iceland over 40 years of age (n = 148,711) were offered participation with 75,422 (51%) were screened using serum protein electrophoresis (SPEP) and free light chain (FLC) analysis. The 3,725 with abnormal screening were randomized to one of the three arms of the study, and bone marrow sampling was performed in over 1,600 individuals. The iStopMM study started in 2016 and is still ongoing. First results from the screening show that the prevalence of MGUS is 4.5% and the prevalence of SMM is 0.5% in individuals over 40 years old, both conditions are more common in men than women and the prevalence increases with age. Around one third of the SMM patients have intermediate- to high-risk SMM according to the Mayo Clinic 20/2/20 risk stratification model, and could potentially be candidates for early treatment. Furthermore, initial results from the randomized clinical trial show that active screening identified significantly higher number of individuals with full-blown malignancy (MM and related disorders) than in the control arm. These first results show that screening is feasible, however, until the final results from the iStopMM study become available, including overall survival data, data on MM related organ damage and quality of life, we advise against systematic MGUS screening in healthy individuals.
Heterogeneity of treatment effects by risk in pulmonary arterial hypertension
Authors: Hao-Min Pan, Robyn L. McClelland, Jude Moutchia, Dina H. Appleby, Jason S. Fritz, John H. Holmes, Jasleen Minhas, Harold I. Palevsky, Ryan J. Urbanowicz, Steven M. Kawut, Nadine Al-Naamani
Journal: European Respiratory Journal (2023)

Background It is currently unknown if disease severity modifies response to therapy in pulmonary arterial hypertension (PAH). We aimed to explore if disease severity, as defined by established risk-prediction algorithms, modified response to therapy in randomised clinical trials in PAH. Methods We performed a meta-analysis using individual participant data from 18 randomised clinical trials of therapy for PAH submitted to the United States Food and Drug Administration to determine if predicted risk of 1-year mortality at randomisation modified the treatment effect on three outcomes: change in 6-min walk distance (6MWD), clinical worsening at 12 weeks and time to clinical worsening. Results Of 6561 patients with a baseline US Registry to Evaluate Early and Long-Term PAH Disease Management (REVEAL 2.0) score, we found that individuals with higher baseline risk had higher probabilities of clinical worsening but no difference in change in 6MWD. We detected a significant interaction of REVEAL 2.0 risk and treatment assignment on change in 6MWD. For every 3-point increase in REVEAL 2.0 score, there was a 12.49 m (95% CI 5.86–19.12 m; p=0.001) greater treatment effect in change in 6MWD. We did not detect a significant risk by treatment interaction on clinical worsening with most of the risk-prediction algorithms. Conclusions We found that predicted risk of 1-year mortality in PAH modified treatment effect as measured by 6MWD, but not clinical worsening. Our findings highlight the importance of identifying sources of treatment heterogeneity by predicted risk to tailor studies to patients most likely to have the greatest treatment response.
P62 USE OF ANTIVIRAL FOR PAUCISINTOMATIC COVID-19 INFECTION IN MULTIPLE MYELOMA PATIENTS UNDERGOING TREATMENT
Authors: O. Annibali, Fazio F, Di Cecca M, Liberatore C, Pisani F, De Padua L, Tomarchio V, Poggiali R, Fioritoni F, Tafuri MT, Viola F, Montanaro G, Passucci M, Pulini S, Petrucci MT, Rigacci L
Journal: HemaSphere (2023)

Patients with multiple myeloma are at increased risk of mortality from COVID-19 infection and show a lower rate of sieroconversion after vaccination and usually late negativization. In this regard, some studies have shown slight changes in mortality during the post-vaccine era. COVID-19 infection, during treatment creates several issues such as discontinuation of active treatment for the disease and a rapid negativization is useful to allow early resumption of therapy. From February 2022, it is possible to set up antiviral treatment with Nirmatrelvir or Molnupiravir in paucisymptomatic patients by reducing hospitalization and evolution in more severe infection. In this study, we collect data on 75 patients with active Multiple Myeloma and COVID-19 infection from Center District (Lazio, Umbria, Marche, Abruzzo) to evaluate the efficacy of this treatment. Of 75 pts, 57 (76%) were in first line of treatment and 18 (24%) in different lines; 62 (82.6%) were treated with antivirals, specifically 49 (65%) with oral antivirals (Nirmartelvir or molnupinavir) and 14 (18.6%) with intravenous antivirals (remdesivir); the remaining 13 (17.4%) patients had no treatment. Of the 62 patients treated with antivirals, 14 (22.6%) were hospitalized for worsening general condition, and 5 (8%) died. This group of patients resolved the infection with swab negativization with a median of 10 days (range 4-72) while the 13 patients who did not undergo any antiviral treatment presented a median of negativization of 15 days. (range 5-20). The majority of patients (67/75 subjects; 89%) had been vaccinated with at least two doses of mRNA vaccine; of these, 54 patients were treated with antivirals presenting a median time to negativization of 9 days compared with 16 days for the unvaccinated and antiviral-treated (P=NS). No difference in hospitalization and mortality. Mortality from COVID-19 infection in the sample was 8% (6/75). In conclusion despite the limitations of the sample size, the use of antivirals in patients with multiple myeloma under active treatment seems to offer a more rapid negativization of the infection promoting a rapid resumption of chemotherapy treatment despite an important effect on mortality and hospitalization. A larger sample will be useful in providing further information on mortality and hospitalization in this patient setting
Biomedical applications of magnetosomes: State of the art and perspectives
Authors: Gang Ren, Xia Zhou, Ruimin Long, Maobin Xie, Ranjith Kumar Kankala, Shibin Wang, Yu Shrike Zhang, Yuangang Liu
Journal: Bioactive Materials (2023)

Magnetosomes, synthesized by magnetotactic bacteria (MTB), have been used in nano- and biotechnological applications, owing to their unique properties such as superparamagnetism, uniform size distribution, excellent bioavailability, and easily modifiable functional groups. In this review, we first discuss the mechanisms of magnetosome formation and describe various modification methods. Subsequently, we focus on presenting the biomedical advancements of bacterial magnetosomes in biomedical imaging, drug delivery, anticancer therapy, biosensor. Finally, we discuss future applications and challenges. This review summarizes the application of magnetosomes in the biomedical field, highlighting the latest advancements and exploring the future development of magnetosomes.
Progress Toward Poliomyelitis Eradication — Worldwide, January 2021–March 2023
Authors: Scarlett E. Lee, Sharon A. Greene, Cara C. Burns, Graham Tallis, Steven G. F. Wassilak, Omotayo Bolu
Journal: MMWR Morbidity and Mortality Weekly Report (2023)

Since the World Health Assembly established the Global Polio Eradication Initiative (GPEI) in 1988, two of the three wild poliovirus (WPV) serotypes (types 2 and 3) have been eradicated, and global WPV cases have decreased by more than 99.9%. Afghanistan and Pakistan remain the only countries where indigenous WPV type 1 (WPV1) transmission has not been interrupted. This report summarizes progress toward global polio eradication during January 1, 2021-March 31, 2023, and updates previous reports (1,2). In 2022, Afghanistan and Pakistan reported 22 WPV1 cases, compared with five in 2021; as of May 5, 2023, a single WPV1 case was reported in Pakistan in 2023. A WPV1 case was reported on the African continent for the first time since 2016, when officials in Malawi confirmed a WPV1 case in a child with paralysis onset in November 2021; neighboring Mozambique subsequently reported eight genetically linked cases. Outbreaks of polio caused by circulating vaccine-derived polioviruses (cVDPVs) can occur when oral poliovirus vaccine (OPV) strains circulate for a prolonged time in underimmunized populations, allowing reversion to neurovirulence (3). A total of 859 cVDPV cases occurred during 2022, an increase of 23% from 698 cases in 2021. cVDPVs were detected in areas where poliovirus transmission had long been eliminated (including in Canada, Israel, the United Kingdom, and the United States). In addition, cocirculation of multiple poliovirus types occurred in multiple countries globally (including Democratic Republic of the Congo [DRC], Israel, Malawi, Mozambique, Republic of the Congo, and Yemen). The 2022-2026 GPEI strategic plan targeted the goal of detecting the last cases of WPV1 and cVDPV in 2023 (4). The current global epidemiology of poliovirus transmission makes the likelihood of meeting this target date unlikely. The detections of poliovirus (WPV1 and cVDPVs) in areas where it had been previously eliminated underscore the threat of continued poliovirus spread to any area where there is insufficient vaccination to poliovirus (3). Mass vaccination and surveillance should be further enhanced in areas of transmission to interrupt poliovirus transmission and to end the global threat of paralytic polio in children.
Extracellular vesicles in fatty liver promote a metastatic tumor microenvironment
Authors: Zhijun Wang, So Yeon Kim, Wei Tu, Jieun Kim, Alexander Xu, Yoon Mee Yang, Michitaka Matsuda, Lien Reolizo, Takashi Tsuchiya, Sandrine Billet, Alexandra Gangi, Mazen Noureddin, Ben A. Falk, Sungjin Kim, Wei Fan, Mourad Tighiouart, Sungyong You, Michael S. Lewis, Stephen J. Pandol, Dolores Di Vizio, Akil Merchant, Edwin M. Posadas, Neil A. Bhowmick, Shelly C. Lu, Ekihiro Seki
Journal: Cell Metabolism (2023)
Remodeling of the immune and stromal cell compartment by PD-1 blockade in mismatch repair-deficient colorectal cancer
Authors: Jianxia Li, Cheng Wu, Huabin Hu, Ge Qin, Xueqian Wu, Fan Bai, Jianwei Zhang, Yue Cai, Yan Huang, Chao Wang, Jiaqi Yang, Yizhao Luan, Zehang Jiang, Jiayu Ling, Zehua Wu, Yaoxu Chen, Zhi Xie, Yanhong Deng
Journal: Cancer Cell (2023)
A dynamical systems approach for multiscale synthesis of Alzheimer’s pathogenesis
Authors: Jennifer Rollo, John Crawford, John Hardy
Journal: Neuron (2023)

Alzheimer's disease (AD) is a spatially dynamic pathology that implicates a growing volume of multiscale data spanning genetic, cellular, tissue, and organ levels of the organization. These data and bioinformatics analyses provide clear evidence for the interactions within and between these levels. The resulting heterarchy precludes a linear neuron-centric approach and necessitates that the numerous interactions are measured in a way that predicts their impact on the emergent dynamics of the disease. This level of complexity confounds intuition, and we propose a new methodology that uses non-linear dynamical systems modeling to augment intuition and that links with a community-wide participatory platform to co-create and test system-level hypotheses and interventions. In addition to enabling the integration of multiscale knowledge, key benefits include a more rapid innovation cycle and a rational process for prioritization of data campaigns. We argue that such an approach is essential to support the discovery of multilevel-coordinated polypharmaceutical interventions.
Empiric anti-anaerobic antibiotics are associated with adverse clinical outcomes in emergency department patients
Authors: Robert F.J. Kullberg, Michiel Schinkel, W. Joost Wiersinga
Journal: European Respiratory Journal (2023)

<b>In a retrospective cohort of 15 908 emergency department patients, empiric use of anti-anaerobic antibiotics was associated with decreased overall and infection-free survival in patients with suspected infection in the emergency department</b>https://bit.ly/3TRbE0F
Reply to: Anti-anaerobic antibiotics: indication is key
Authors: Rishi Chanderraj, Jennifer M. Baker, Stephen G. Kay, Christopher A. Brown, Kevin J. Hinkle, Daniel J. Fergle, Roderick A. McDonald, Nicole R. Falkowski, Joseph D. Metcalf, Keith S. Kaye, Robert J. Woods, Hallie C. Prescott, Michael W. Sjoding, Robert P. Dickson
Journal: European Respiratory Journal (2023)

<b>A recent @ERSpublications study showed that in critically ill patients and animal models, anti-anaerobic antibiotics increase risk of mortality. The study9s authors explain why they believe this signal is both real and important for the field.</b>https://bit.ly/3KgArYT